A. Ligeiro de Oliveira

Role of sex hormones in allergic inflammation in mice

Background A number of clinical studies have documented both a pro‐ and anti‐inflammatory role for sex hormones in the context of lung inflammation and worsening of asthma.

Low level laser therapy (LLLT) decreases pulmonary microvascular leakage, neutrophil influx and IL-1beta levels in airway and lung from rat subjected to LPS-induced inflammation.

Background and ObjectiveLow level laser therapy (LLLT) is a known anti-inflammatory therapy. Herein we studied the effect of LLLT on lung permeability and the IL-1β level in LPS-induced pulmonary inflammation.Study Design/MethodologyRats were divided into 12 groups (n = 7 for each group). Lung permeability was measured by quantifying extravasated albumin concentration in lung homogenate, inflammatory cells influx was determined by myeloperoxidase activity, IL-1β in BAL was determined by ELISA and IL-1β mRNA expression in trachea was evaluated by RT-PCR. The rats were irradiated on the skin over the upper bronchus at the site of tracheotomy after LPS.ResultsLLLT attenuated lung permeability. In addition, there was reduced neutrophil influx, myeloperoxidase activity and both IL-1β in BAL and IL-1β mRNA expression in trachea obtained from animals subjected to LPS-induced inflammation.ConclusionLLLT reduced the lung permeability by a mechanism in which the IL-1β seems to have an important role.

Subchronic effects of nasally instilled diesel exhaust particulates on the nasal and airway epithelia in mice

Diesel exhaust is the major source of ultrafine particles released during traffic-related pollution. Subjects with chronic respiratory diseases are at greater risk for exacerbations during exposure to air pollution. This study evaluated the effects of subchronic exposure to a low-dose of diesel exhaust particles (DEP). Sixty male BALB/c mice were divided into two groups: (a) Saline: nasal instillation of saline (n = 30); and (b) DEP: nasal instillation of 30 µg of DEP/10 µl of saline (n = 30). Nasal instillations were performed 5 days a week, over 30 and 60 days. Animals were anesthetized with pentobarbital sodium (50 mg/kg intraperitoneal [i.p.]) and sacrificed by exsanguination. Bronchoalveolar lavage (BAL) fluid was performed to evaluate the inflammatory cell count and the concentrations of the interleukin (IL)-4, IL-10, and IL-13 by enzyme-linked immunosorbent assay (ELISA). The gene expression of oligomeric mucus/gel-forming (Muc5ac) was evaluated by real-time polymerase chain reaction (PCR). Histological analysis in the nasal septum and bronchioles was used to evaluate the bronchial and nasal epithelium thickness as well as the acidic and neutral nasal mucus content. The saline group (30 and 60 days) did not show any changes in any of the parameters. However, the instillation of DEP over 60 days increased the expression of Muc5ac in the lungs and the acid mucus content in the nose compared with the 30-day treatment, and it increased the total leukocytes in the BAL and the nasal epithelium thickness compared with saline for 60 days. Cytokines concentrations in the BAL were detectable, with no differences among the groups. Our data suggest that a low-dose of DEP over 60 days induces respiratory tract inflammation.

Effects of single or repeated amphetamine treatment and withdrawal on lung allergic inflammation in rats

The effects of single or repeated amphetamine (AMPH) treatment and those of AMPH withdrawals on immune-mediated lung inflammatory response were studied in rats. Two experiments were done. In the first, rats egg-albumin (OVA) sensitized were singularly or repeatedly (21 days, once daily) treated with AMPH (1.0 mg/kg) or with a similar number and volume of 0.9% NaCl. The OVA aerosol challenge was performed 12 h after the single or last repeated AMPH treatment and also 72 and 120 h after AMPH withdrawal. In the second experiment, the effects of reserpine (1.0 mg/kg/day for 5 consecutive days) on single AMPH actions on lung allergic response of rats were analyzed. Single and repeated AMPH treatment induced opposite actions on Bronchoalveolar lavage fluid (BAL) cellularity of allergic rats: single treatment decreased and repeated treatment increased the total number of cells as well as those of macrophages, neutrophils and eosinophils. Our data also showed that single but not repeated AMPH treatment decreased the number of neutrophils, monocytes and lymphocytes in the peripheral blood, and increased the total number of bone marrow cells in rats sensitized and challenged with OVA. Furthermore, it was shown that reserpine treatment precluded the effects of single AMPH treatment on cellular migration to the lung of OVA-sensitized and challenged rats. It was concluded that AMPH effects on lung inflammatory response and cell recruitment to the lung in allergic rats rely at least partially on corticosterone serum levels. The possible involvement of vesicular monoamine transporter type 2 (VMAT2) with these observed effects was discussed.

44. Cohabitation with a sick-cage mate exacerbates allergic lung inflammatory response in mice

The objective of this study was analyze the effects of cohabitation with sick partner on allergic lung inflammatory response in ovalbumin (OVA) sensitized and challenged mice. Pairs of mice were divided into control and experimental groups. Within each group, one mouse from each pairs was immunized with a solution containing (OVA). The remaining mouse from the experimental group was injected with Ehrlich tumor cells being designated as “companion of sick partner” (CSP); the remaining mouse of the control group was injected with PBS being designated as “companion of healthy partner” (CHP). CSP mice presented in relation to CHP mice: increased number of eosinophils and neutrophils in the BAL; increased IL-4 and IL-5 levels and decreased IL-10 and INF-γ in the BAL supernatant; increased IgG1-OVA and decrease IgG2a-OVA levels on peripheral blood; increased expression of L-selectin in the BAL granulocytes; decreased in vitro tracheal reactivity to metacholine; no changes on plasma corticosterone levels and increased levels of plasmatic noradrenaline. The results suggest that the exacerbation of the allergic lung inflammatory response in CSP mice is a consequence of the psychological stress induced by forced long-term cohabitation with sick the partner, a fact that might ultimately depend on the changes induced by catecholamines on Th1/Th2 balance, toward a Th2 cytokine profile and finally the recruitment and activation of eosinophils in the airways. FAPESP: 2012/03372-3; 2009/51886-3.